Synergistic combinations of 4,5-dichloro-2-n-octyl-3-isothiazolone or 2-methyl-3-isothiazolone with ferric dimethyl dithiocarbamate fungicide

ABSTRACT

A synergistic antimicrobial composition comprising 4,5-dichloro-2-n-octyl-3-isothiazolone or 2-methyl-3-isothiazolone and ferric dimethyldithiocarbamate, in a ratio to each other which exhibits synergism is disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to antimicrobial compositions and methodsof controlling microbials.

2. Description of the Prior Art

The presence of microbes in various aqueous systems such as latices,paints, coatings, cooling water systems, decorative ponds and the like,can cause deterioration or disfigurement of these systems. For example,painted surfaces may be disfigured by the unsightly buildup of microbes,thus detracting from the overall aesthetics of the painted article;cooling towers may lose efficiency due to the buildup of microbes onsurfaces, thus reducing the heat transfer capabilities of the tower. Itis conventional to practice methods which inhibit the microbialdeterioration of such systems by incorporating a variety of additives orcombination of additives that are characterized by having antimicrobialactivity.

A wide variety of materials have been used to control microbes indifferent environments, some of which are: chlorine/bromine compounds,glutaraldehyde, isothiazolones, organotin formulations, copper salts,quaternary ammonium compounds (SD Strauss and PR Puckorius in J. Power,S1, June 1984), and triazines. Each has deficiencies related totoxicity, pH and temperature sensitivity, limited effectiveness,chemical stability, and/or compatibility.

Ferric dimethyldithiocarbamate is a known agricultural fungicide. Basedon the aforementioned performance deficiencies of conventionalantimicrobial compounds there is a need for more effective antimicrobialagents that can be used at lower dosage rates, thus being more costeffective for the end user, reducing the pollution load on the affectedenvironmental systems, and reducing the side effects to nearbynon-target organisms, such as fish, useful crops, etc.

SUMMARY OF THE INVENTION

It is an object of this invention to provide a method of controllingmicrobes at very low levels of active ingredient. It is a further objectto use compositions which are compatible with a variety of systemssusceptible to deterioration by microbes. Another object is to provide amethod of controlling microbes in cooling towers, paints, marineantifoulant coatings, spray washes, swimming pools, coatings, decorativeponds, fabric, leather, paper, wood, metal working fluids, fuel systems,and the like, without objectionable by-product odors, discoloration, orotherwise detrimental effects on the treated (and controlled) systems.These objects, and others which will become apparent from the followingdisclosure, are achieved by the present invention which is, in oneaspect a composition useful for controlling microbes comprising (A)4,5-dichloro-2-n-octyl-3-isothiazolone or 2-methyl-3-isothiazolone and(B) ferric dimethyldithiocarbamate, in a ratio to each other whichexhibits synergism.

In another aspect, the invention comprises a method for inhibiting thegrowth of a member selected from the group consisting of bacteria,fungi, algae and mixtures thereof in a locus subject to contamination bysaid member, which comprises incorporating onto or into the locus, in anamount which is effective to adversely affect the growth of said member,the aforementioned composition.

Another aspect of the invention is a method of controlling microbes incooling tower water comprising maintaining a concentration of theaforementioned composition in the water.

The invention also comprises microbe-resistant coating or impregnantcompositions and marine antifoulant compositions comprising theantimicrobial composition.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENT

We have discovered an especially effective composition useful forcontrolling microbes comprising (A) 2-methyl-3-isothiazolone or4,5-dichloro-2-n-octyl-3-isothiazolone and (B) ferricdimethyldithiocarbamate, in a ratio to each other which exhibitssynergism.

In accordance with the invention a method of controlling microbescomprises using an effective amount of the aforementioned composition.

Another important utility is in imparting microbial resistance to acoating or an impregnant composition comprising incorporation of thecomposition of the invention in the coating or impregnant, preferably ata concentration of about 0.1 ppm to about 2 percent, more preferably ata concentration of about 1 ppm to 1 percent, and most preferably at aconcentration of about 10 to 4000 ppm.

Algae-resistant coating or impregnant compositions provided by theinvention preferably comprise about 0.1 ppm to about 2 percent of theantimicrobial composition, more preferably about 10 to 4000 ppm.

In a marine antifoulant composition, on the other hand, theantimicrobial composition of the invention comprises about 1 to 10percent of the antifoulant composition.

In the treatment of metal working fluids; and in the protection offabric, leather, paper or wood materials, the microbicidal compositionis added at a concentration of from about 0.1 ppm to about 2 percent byweight. In aqueous media, the microbicidal composition comprises fromabout 0.1 ppm to about 1 percent of the aqueous system depending on thespecific end use; for example, in cooling water tower applications andwith pulp or paper manufacturing processes, the microbicidal compositionis added at a concentration from about 0.1 to about 1000 ppm by weight.In the treatment of fuel systems, e.g., jet fuel, gasoline, heating oil,etc., the microbicidal composition is added at a concentration of fromabout 0.1 ppm to about 1 percent by weight.

The microbial resistant compositions can also be used in constructionproducts such as stucco, roof mastics, wall mastics, and masonrycoatings for algae protection; in clear finishes and coatings to protectunderlying substrates from algae; for algae control in aquaculture,including aquaria, fish hatcheries, shrimp ponds, finfish ponds, molluscand crustacean cultivation; for algae control in recreational anddecorative bodies of water such as swimming pools, lakes, fountains anddecorative ponds; for algae control in bodies of water for industrial ormunicipal use, such as settling or separation ponds, waste treatmentponds, and water reservoirs; for algae control in hydroponic farming;for algae control in processing and manufacture of pulp and paperproducts; for inclusion in plastics or in coatings for plastics toprotect against algae; and in plastics or coatings for plastics forswimming pool liners.

We prefer antimicrobial compositions wherein the weight ratio of (A) to(B) is about 0.1/100 to about 100/0.1. Particularly preferred ratioranges are from about 0.5/100 to about 10/1 and 1/10 to about 1/10,depending on the isothiazolone used.

The following examples represent just a few of the many uses andcompounds of the invention. They are intended to be illustrative but notlimiting. Various modifications, alternatives, and improvements shouldbecome apparent to those skilled in the art without departing from thespirit and scope of the invention.

EXAMPLES A. General Procedure

MIC values represent the Minimum Inhibitory Concentration. This isdefined as the lowest level of compound required to completely inhibit(repress) the growth of a given organism.

A synergistic effect is defined as the response of two variables whichis greater than the sum of both parts alone. Synergy was determined fromcombination studies with two compounds by the method of calculationdescribed by F. C. Kull, P. C. Eisman, H. D. Sylwestrowicz and R. K.Mayer, Applied Microbiology 9,538 (1961): ##EQU1## where: Q_(A)=quantity of compound A, acting alone, producing an end point (MIC)

Q_(a) =quantity of compound A, in mixture, producing an end point (MIC)

Q_(B) =quantity of compound B, acting alone, producing an end point(MIC)

Q_(b) =quantity of compound B, in mixture, producing an end point (MIC)

The following SI values may be attained:

SI>1 represents antagonistic effect,

SI=1 represents additive effect,

SI<1 represents synergy.

Efficacy studies were conducted on a variety of microorganisms ferricdimethyldithiocarbamate and isothiazolone mixtures. The MIC studies wereconducted using microtiter plate assays. In this method, a wide range ofconcentrations was tested by preparing two-fold serial dilutions of thecompound in 96-well plastic microtiter plates. All liquid mediatransfers were performed with calibrated single or multichannel digitalpipetters. Stock solutions of compounds were prepared in appropriatesolvents and dispensed to the growth medium. All subsequent dilutions inplates were made using the desired growth medium; total volume of liquidin each well was 100 μl. Each plate contained a concentration of bothcompounds made by serially titrating equal volumes of liquids in twodirections in the microtiter plate. Each plate contained a control rowfor each combination (one component only), hence, the individualcompound MIC values were also determined.

B. Isothiazolone Structure

Isothiazolones included in the examples are designated as follows:

1) Isothiazolone A: 4,5-dichloro-2-n-octyl-3-isothiazolone

2) Isothiazolone B: 2-methyl-3-isothiazolone

EXAMPLE 1

Using a pure culture of Aspergillus niger, various combinations ferricdimethyldithiocarbamate and Isothiazolone A were subjected to MICdeterminations in mycophil broth. Compound A is Isothiazolone A andCompound B is ferric dimethyldithiocarbamate.

    ______________________________________                                        Qa             Qb        Qa/Qb    Sl                                          ______________________________________                                        0              64 (Q.sub.B)                                                                            --       1.0                                         0.16           32         1/205   0.56                                        0.16           16         1/99    0.31                                        0.16            8         2/98    0.19                                        0.31           32         1/99    0.62                                        0.31           16         2/98    0.37                                        0.31            8         4/96    0.25                                        0.31            4         7/93    0.19                                        0.31            2        14/86    0.16                                        0.62           32         2/98    0.75                                        0.62           16         4/96    0.5                                         0.62            8         7/93    0.37                                        0.62            4        14/86    0.31                                        0.62            2        24/76    0.28                                        0.62            1        38/62    0.27                                        0.62            0.5      56/44    0.26                                        1.25           16         7/93    0.75                                        1.25            8        14/86    0.62                                        1.25            4        24/76    0.56                                        1.25            2        38/62    0.53                                        1.25            1        56/44    0.52                                        1.25            0.5      71/29    0.51                                        1.25            0.25     83/17    0.5                                         2.5 (Q.sub.A)   0        --       1.0                                         ______________________________________                                    

EXAMPLE 2

Using a pure culture of Pseudomonas aeruginosa, various combinations offerric dimethyldithiocarbamate and Isothiazolone B were subjected to MICdeterminations in mycophil broth. Compound A is Isothiazolone B andCompound B is ferric dimethyldithiocarbamate.

    ______________________________________                                        Qa         Qb          Qa/Qb   Sl                                             ______________________________________                                         0         >500 (Q.sub.B)                                                                            --      1.0                                            16          125        11/89   <0.75                                          16           64        20/80   <0.63                                          16           32        33/67   <0.56                                          16           16        50/50   <0.53                                          16           8         67/33   <0.52                                          16           4         80/20   <0.51                                          16           2         89/11   <0.51                                          32 (Q.sub.A)                                                                               0         --      1.0                                            ______________________________________                                    

We claim:
 1. A microbicidal composition comprising a synergistic mixturea first component of which is selected from the group consisting of4,5-dichloro-2-n-octyl-3-isothiazolone and 2-methyl-3-isothiazolone anda second component of which is ferric dimethyldithiocarbamate, whereinthe ratio of the first component to the second component is in a rangeof from about 0.1/100 to about 100/0.1.
 2. The composition of claim 1wherein the first component is 4,5-dichloro-2-n-octyl-3-isothiazoloneand the ratio of the first component to the second component is in therange from about 0.5/100 to about 10/1.
 3. The composition of claim 1wherein the first component is 2-methyl-3-isothiazolone and the ratio ofthe first component to the second component is in the range from about1/10 to about 10/1.
 4. A coating or impregnant composition comprisingfrom about 0.1 ppm to about 2 percent by weight of the composition ofclaim
 1. 5. A marine antifoulant composition comprising about 1-10percent by weight of the composition of claim
 1. 6. A method forinhibiting the growth of a member selected from the group consisting ofbacteria, fungi, algae and mixtures thereof in a locus subject tocontamination by said member, which comprises incorporating onto or intothe locus, in an amount which is effective to adversely affect thegrowth of said member, the composition of claim
 1. 7. The method ofclaim 6 wherein the locus is an aqueous medium and the composition isused in an amount from about 0.1 ppm to about 1 percent by weight. 8.The method of claim 6 wherein the locus is a coating or impregnantcomposition and the composition of claim 1 is used in an amount fromabout 0.1 ppm to about 2 percent by weight.
 9. The method of claim 6,wherein the locus is a marine antifoulant composition and thecomposition of claim 1 is used in an amount from about 1 to about 10percent by weight.
 10. The method of claim 6 wherein the locus is a pulpor paper manufacturing process and the composition is used in an amountfrom about 0.1 to about 1000 ppm by weight.
 11. The method of claim 6wherein the locus is cooling tower water and the composition is used inan amount from about 0.1 to about 1000 ppm by weight.
 12. The method ofclaim 6 wherein the locus is a metal working fluid and the compositionis used in an amount from about 0.1 ppm to about 2 percent by weight.13. The method of claim 6 wherein the locus is fabric, leather, paper orwood and the composition is used in an amount from about 0.1 ppm toabout 2 percent by weight.
 14. The method of claim 6 wherein the locusis a fuel system and the composition is used in an amount from about 0.1ppm to about 1 percent by weight.